Hermann Linde

Chloroformates and isothiocyanates derived from 2-arylpropionic acids as chiral reagents: synthetic routes and chromatographic behaviour of the derivatives

Chiral derivatization with an enantiomerically pure reagent is an economical and effective way to separate the enantiomers of optically active drugs on achiral HPLC columns. This paper describes the preparation and analytical testing of two novel chiral derivatizing agents (CDAs) deriving from the 2-arylpropionic acid (S)-(+)-naproxen, viz., 1-(6-methoxy-2-naphthyl)ethyl isothiocyanate (NAP-IT) and 2-(6-methoxy-2-naphthyl)-1-propyl chloroformate (NAP-C). Both are suitable reagents for the derivatization of amino compounds (e.g., β-adrenoceptor antagonists, antiarrhythmic agents). The diastereomeric derivatives of these chiral drugs are resolved on reversed-phase HPLC columns and/or silica gel stationary phases. The high UV absorbance and an additional intrinsic fluorescence of both CDAs facilitates the detection of the derivatization products.